1. Field of the Invention
This invention pertains to the monochlorination of methyl groups on pyridine oxides.
2. Description of the Prior Art
Although monochloromethylpyridines are a well-known class of compounds, the most useful member is 2-chloromethylpyridine. A variety of processes have been used to prepare these compounds.
Chloromethylpyridine compounds have been formed by the reaction of pyridine oxide compounds with certain chlorinating agents. The usual means of chlorinating pyridine oxide is with phosphorus pentachloride or phosphoryl chloride, resulting in a mixture of 2- and 4-chloromethylpyridines. Another process is the direct chlorination of 2-picoline, but the product is contaminated by di- and trichloromethylpyridines.
T. Kato described the reaction of .alpha.-picoline-1-oxide with phosphoryl chloride in Yakugaku Zasshi, 75, 1239 (1955) C.A. 50:8,665h (1956). The reaction was run neat at temperatures of 100.degree. C.-140.degree. C. After removing the phosphoryl chloride, the residue was neutralized with potassium carbonate and extracted with ethyl ether. Only trace amounts of 2-chloromethylpyridine were obtained.
E. Matsumura, J. Chem. Soc. (Japan) 74,363 (1953) C.A. 48:6,422b (1954), described the formation of monochloromethylpyridines from the reaction of 2-picoline-1-oxide with p-toluenesulfonyl chloride.
Mathis et al. (U.S. Pat. No. 3,123,608) described a process for chlorinating side-chain groups by reacting methylpyridines with chlorine. Stepwise chlorination to mono-, di- and trichloromethyl derivatives depended upon the following conditions: (1) reaction temperature between 40.degree. C. and 80.degree. C., (2) inert diluent as a solvent, and (3) an inorganic hydrochloric acid binding agent. However, the yield of 2-picolyl chloride obtained from this process was only 65 percent of theory. Di- and trichloromethylpyridine were also formed by contaminating by-products.
Side-chain chlorination of methylpyridines was discussed by Hattori et al. in Japanese Patent No. 74 127,977; C.A. 84:121,665p (1975). Water and a hydrochloric acid acceptor were present in an inert solvent. The compound 2-picoline was chlorinated to 2-(chloromethyl) and 2-(dichloromethyl) pyridine following this process.